Giovanna Spatari

Markers of Endothelial and Platelet Status in Patients with Essential Thrombocythemia and Polycythemia Vera.

Vascular complications are the main cause of morbidity in polycythemia vera (PV) and essential thrombocythemia (ET). To investigate plasma concentrations of soluble P-selectin (sP-Sel.), soluble E-selectin (sE-Sel.) and soluble thrombomodulin (sTM) in relation to the presence of thromboembolic events 38 patients with Chronic Myeloproliferative Disorders (CMD) (14 PV pts and 24 ET pts), 15 age-matched controls and 15 patients with secondary thrombocytosis were studied. Plasma levels of P-Sel., E-Sel. and TM were significantly increased in the group of patients as compared with control subjects (respectively p < 0.001, p < 0.04 and p < 0.01). sP-Sel. levels showed no significant difference between the patients and those with secondary thrombocytosis. No difference in sP-sel levels were also observed between subgroups of CMD patients with and without vascular complications. However, among patients with ET, those with thrombosis had higher sP-Sel levels than those without thrombosis (1.177 ± 110.48 ng/ml vs 816.25 ± 99.27 ng/ml). High levels of sE-Sel and sTM were found in CMD patients (71.93 ± 39.08 ng/ml and 35.81 ± 20.79 ng/ml, respectively). Plasma sE-Sel. concentration was significantly higher in CMD patients with thrombosis than that in CMD patients without thrombosis (p < 0.001). There was no difference in sTM concentration between two groups. These findings indicate that sustained endothelium and platelet activation is present in patients with ET and PV and it might contribute to the pathogenesis of thromboembolic events in these patients.

Neurocognitive effects in welders exposed to aluminium

Objectives: Various authors who studied the effects of aluminium (Al) exposure on the neurocognitive system in the last 30 years have reached different and often contradictory conclusions. The aim of this study is to help clarify the effects that the metal causes on cognitive ability in a group of naval welders exposed to Al. Methods: The study was performed on a sample of 86 male Al welders in a shipyard in Messina. The average value of environmental Al, recorded in the workplace, was 19.5 mg/m3. The blood levels of Al, zinc, manganese, lead and chromium were monitored in all the subjects. The reagents used for the neuropsychic study were the Wechsler Memory Scale (WMS), the Colour Word Test or Stroop Test and the Test of Attention Matrixes. The results were compared with those obtained in a similar control group not exposed to Al and with an Al-b value of 6.93 g/l. Results: For all the mental reagents used, the reply is obtained in the sample of exposed subjects showed decreased cognitive response with regard to attention and memory performance. The comparison between the individual tests showed greater sensitivity of performance studied using the WMS and the Stroop Test compared with the Test of Attention Matrixes. The alterations encountered in the cognitive functions studied increased proportionally to time of exposure and quantity of metal absorbed. Conclusion: The study confirmed that occupational exposure to Al causes alteration in cognitive responses that are more evident in complex functions.

Influence of glutathione S-transferases polymorphisms on biological monitoring of exposure to low doses of benzene

The environmental and biological monitoring of benzene exposure is crucial to prevent the toxic effects of this solvent in workers. The degree of correlation, however, between the two and of different biomarkers among them varies, particularly at low levels of exposure, depending on various factors, including variability in metabolizing enzymes and smoking habits. To investigate these further, a cohort of 28 petrochemical workers (6 smokers and 22 non smokers) was monitored throughout ten consecutive days, on two occasions, two years apart, by collecting in total 173 environmental and biological samples. The airborne benzene levels, the urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA) concentrations, and the glutathione S-transferases (GST) M1 and T1 genotypes were measured. S-PMA was the only metabolite statistically correlated with airborne benzene levels (r=0.447, P<0.0001), particularly in non smokers (r=0.667, P<0.0001), the smoking habit being the only variable influencing metabolite excretion. Finally, a reduced S-PMA excretion was found to be associated with the GSTT1, but not the GSTM1, null genotype. In conclusion, the results show that S-PMA, but not t,t-MA, is able to monitor exposure to low benzene concentrations and confirm that the GSTT1 null genotype has a significant influence on metabolite excretion. The influence of the GSTT1 null genotype, however, was low, even when studying each subject with several urine samples.

Increase of novel biomarkers for oxidative stress in patients with plasma cell disorders and in multiple myeloma patients with bone lesions

ObjectivesProtein oxidation plays a key role in the pathogenesis of oncological diseases. In this study, we analyzed the oxidative stress in untreated multiple myeloma (MM) patients and in patients affected by monoclonal gammopathy of uncertain significance (MGUS).MethodsWe evaluated serum levels of advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs), and protein nitrosylation in patients with monoclonal gammopathy and in control subjects.ResultsSerum levels of AOPPs and S-nitrosylated proteins were significantly increased in MM patients in comparison to controls and to MGUS subjects. Moreover, in MM patients the levels of AOPPs, AGEs and S-nitrosylated proteins were significantly higher in patients with bone lesions compared with those without lytic bone lesions.ConclusionsMM is closely associated with oxidative stress and further investigation might provide an insight to understand a putative causal link between oxidative stress and MM disease onset and progression or MM complications.

Relationship Between Advanced Oxidation Protein Products, Advanced Glycation End Products, and S-Nitrosylated Proteins With Biological Risk and MDR-1 Polymorphisms in Patients Affected by B-Chronic Lymphocytic Leukemia

The aim of our study was to analyze the serum levels of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs), and protein nitrosylation in patients with B-chronic lymphocytic leukemia (B-CLL). AOPPs, AGEs, and S-nitrosylated were increased in B-CLL patients. The mutation of IgVH gene, CD 38, and Zap 70 expression were not associated with increased oxidative stress. The mutant 2677GT genotype was found to be associated with higher AGEs levels with respect to wild-type genotype, while as far the C3435T MDR1 polymorphism is concerned, subjects presenting wild-type genotype showed higher values of AOPPs with respect to heterozygous genotype. Our results suggest that B-CLL is associated with oxidative stress.

Serum levels of carbonylated and nitrosylated proteins in mobbing victims with workplace adjustment disorders

AIM Today the most important problem in the work place is psychological abuse, which may affect the health because of high levels of stress and anxiety. There is evidence that most psychiatric disorders are associated with increased oxidative stress but nothing is reported about the presence of oxidative stress in mobbing victims. METHODS This study has been carried out in a group of 19 patients affected by workplace mobbing-due adjustment disorders, in comparison with 38 healthy subjects, to evaluate whether oxidative stress may be induced by mobbing. RESULTS Serum levels of protein carbonyl groups and of nitrosylated proteins, biological markers of oxidative stress conditions, were higher than those measured in healthy subjects. CONCLUSIONS These findings may contribute to a better understanding of the redox homeostasis dysregulation occurring in victims of workplace mobbing.

Increased concentration of circulating acid glycosaminoglycans in chronic lymphocytic leukaemia and essential thrombocythaemia

To verify whether the increase in the number of circulating blood cells that synthesize glycosaminoglycans, B-lymphocytes or platelets, in proliferative disorders, may be associated with changes in the circulation of acid glycosaminoglycans, the serum and plasma concentrations of these polysaccharides have been measured in terms of their sugar components, following isolation and purification by chromatographic methods, in patients with chronic lymphocytic leukaemia or with essential thrombocythaemia and in healthy controls. In the patients, the concentrations of total circulating glycosaminoglycans and of both glucosamine-containing and galactosamine-containing serum glycosaminoglycans were significantly higher than in controls. These concentrations did not significantly correlate with the number of lymphocytes in patients with chronic lymphocytic leukaemia and of platelets in patients with essential thrombocythaemia. Analytical data suggest that excess glycosaminoglycans are mainly composed of chondroitin sulphate molecules and contain heparan sulphate structures.

Changes in advanced oxidation protein products, advanced glycation end products, and s-nitrosylated proteins, in patients affected by polycythemia vera and essential thrombocythemia.

OBJECTIVES Oxidative stress has a clear pro tumoral effect in myeloproliferative neoplasms (MPDs). In this study, we analyzed oxidative stress in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Design and methods We analyzed serum levels of advanced oxidation protein products (AOPPs) degradation, advanced glycation end products (AGEs), and protein nitrosylation in ET and PV patients. We also evaluated neutrophil gelatinase-associated lipocalin (NGAL) levels, an acute phase protein isolated in human neutrophils, the activation status of platelets and leukocytes, and the JAK2 (V617F) mutation status. RESULTS AOPPs and s-nitrosylated proteins were significantly higher in PV and ET subjects as compared to healthy volunteers, while AGEs were higher in ET subjects with respect to controls. Moreover, in PV patients we found a correlation between s-nitrosylated proteins and Hb value. In ET patients AGEs were significantly higher in patients with thrombosis compared with those without thrombotic events. CONCLUSIONS Our results suggest that oxidative stress could play a role in the physiopathology of MPDs and in the onset of myeloproliferative associated thrombotic risk.

Increased serum levels of advanced oxidation protein products and glycation end products in subjects exposed to low-dose benzene

Simple aromatic hydrocarbon benzene occurs naturally in crude oil and petroleum. Benzene has been internationally recognised as a haematotoxin and carcinogen. The involvement of oxidative stress is a major susceptibility factors for benzene hematotoxicity in humans. Advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs) are modified structures which can serve as markers of oxidative stress. The aim of this study is to assess modification of circulating AOPPs and AGEs, as early markers of oxidative stress, in subjects exposed to low dose of benzene. Furthermore the genetic polymorphism of glutathione-S-transferase (GST) may be related to health effects of benzene exposure, in fact both genotype T1 (GSTT1) and M1 (GSTM1) are involved in the detoxification of benzene oxide. The study was performed on 54 workers oil refinery employees. A group of 32 healthy age-matched subjects was included as controls. The AOPPs serum levels in oil refinery employees were higher in a statistically significant way than those measured in controls, but there were no significant changes in serum AGE levels between both groups. However, GST polymorphisms had not influence on serum levels of both biomarkers, so demonstrating that production of circulating AGEs and AOPPs in benzene parity-exposed workers levels is not dependent by GST genotypes. We can conclude that, in this condition, AOPPs are more sensitive marker of low benzene exposure than AGEs.

Virological profiles in hepatitis B virus inactive carriers: monthly evaluation in 1-year follow-up study

Abstract: Study subject: We longitudinally evaluated the virological behaviour and the hepatitis B virus (HBV) genomic variability in inactive HBV surface antigen (HBsAg) chronic carriers.